SUMMARY OF SAFETY AND EFFECTIVENESS (SSED)

1. GENERAL INFORMATION

Device Generic Name: Monofocal Posterior Chamber Intraocular Lens (lOL)

Device Trade Name: iSphericTM Model YA-60BB Intraocular Lcns

Applicant's Name and Address: Hoya Surgical Optics14768 Pipeline AvenueChine Hills, CA 91709

Date(s) of Panel Recommendation: Not Applicable

Premarket Approval Application (PMIA) Number: P080004

Date of FDA Notice of Approval: September 26, 2008

Expedited: Not applicable

II. INDICATIONS FOR USE

The Hoya iSpheric TM Model YA-60BB Intraocular Lens is indicated for primaryimplantation in the capsular bag of the eye for the visual correction of aphakia in adultpatients in whom a cataractous lens has been removed.

III. CONTRAINDICATIONS

No absolute contraindications are known.

IV. WARNINGS AND PRECAUTIONS

The warnings and precautions can be found in the iSpheric'. M odel YA-60BBIntraocular Lens labeling.

V. DEVICE DESCRIPTION

Tlhe 1ova iSpheric'T Model YA-60BB Intraocular Lens (LOL). is an ultraviolet absorbingposterior chamber intraocular lens designed to be implanted posterior to the Mirs where thelens will replace the optical function of the natural crystalline lens. I lowever,accommodation will not be replaced. '[he lens has a foldable UV-absorbing acrylic opticwit ti a 6.0 mm diameter. The acrylic optic material blocks approximately 95%/0 ofultraviolet light and has an additional yellow tint added to absorb most visible blue light.The optic thus has a characteristically yellowish tint. The haptics of the I loxa iSpheric 'Model YA-60BB 10I. are made from polyniethyhniethacrylate (PMMA) which has beenbonded to the optic. The haptics are tinted hI Lie to make them easier for the surgeon tovisualize during surgery and have a 5° angulfation. The overall diameter of the lens is12.5 rnm1. 'lhe lens is provided in a Tyvek pouch which has been sterilized using

PMA P080004: FDA Summary of Safety and I{ffectiveness Data page 1

ethylene oxide gas. In the U.S. IDEI study all lenses were folded using forceps duringsurgery to allow insertion of the lens through a small incision following cataractextraction. The Hoya iSpheric' m Model YA-60BB Intraocular Lens is intended to beplaced in the posterior chamber of the eye entirely within the capsular bag. The Hoya

TMiSpheric Model YA-60BB will be marketed in 0.5 diopters (D) increments from 6.0 to30.0 D.

VI. ALTERNATIVE PRACTICES AND PROCEDURES

There are several other alternatives for the correction of aphakia after cataract surgery.Each alternative has its own advantages and disadvantages. A patient should fullydiscuss these alternatives with his/her physician to select the method that best meetsexpectations and lifestyle.

1. Other approved iOLs may be used for visual correction after cataract surgery.

2. The following are non-surgical alternatives to implantation of an intraocular lensfollowing cataract extraction:

i. Spectacles: Spectacles, or eyeglasses, are the safest means for improving visionafter cataract surgery. However, they are rarely used after modern cataractsurgery as the lenses are required to be thick, which causes distorted vision andmay be uncomfortable or cosmetically unappealing to the patient.

ii. Contact lenses: Contact lenses are rarely prescribed for patients after cataractextraction, although they may provide excellent vision. Contact lenses have risksassociated with their use including infection.

VII. MARKETING HISTORY

The iSphcric'" Model YA-60BB [01. was introduced into the European Union in 2003and into Japan in 2004. The lens is also marketed in Korea, the Republic of China,Singapore, Thailand and Malaysia. The lens has not been withdrawn from any market forreasons related to safety and cl'ectiveness of the device.

VIII. POTENTIAL ADVERSE EFFECTS OF TIlE DEVICE ON HEALTH

Potential adverse events and complications accompanying cataract or implant surgerymay include, but are not limited to the following: corneal endothelial damage, infection(endophthalnitis), retinal detachment, vitritis, cystoid macular edema, corneal edema,pupillary block, cyclitic membrane, iris prolapse, hypopyon. transient or persistentglaucoma and secondary surgical intervention. Secondary surgical interventions include,but are not limited to, lens repositioning, lens replacement, vitreous aspirations oriridectomy lb r pupLillary block. wotid beak repair, and retinal cletachment repair.Amongst those directly related to the 101e are decentering and subluxation, precipitateson the surface of the IOL. Silicone oil. palticcularly when used in tleC surgical treatment ofdetached reti na, may stick to the I(I if the posterior capsule ofl the crystalline Iens is notintact.

PMA P080004: FDA Summnary of Safety and Eflectiveness Data page 2

Other potential adverse events which may accompany cataract or implant surgeryinclude, but are not limited to, the following: nonpigmented precipitates, lens epithelialcell on-growth, vitreous wick syndrome, iris prolapse, acute corneal decompensation andpupillary membrane. No cases of acute corneal decompensation were reported in thisstudy.

Potential secondary surgical interventions that have been associated with intraocularlenses include, but are not limited to, the following: Vitreous aspiration or iridectomy forpupillary block, wound leak repair, retinal detachment repair, lens repositioning due tocorneal touch, corneal transplant. and lens replacement due to refractive error or severeinflammation.

For the specific adverse events that occurred in the clinical studies, please see Section Xbelow.

IX. SUMMARY OF PRECLINICAL STUDI)ESHoya Surgical Optics performed non-clinical studies on this device in accordance with theISO 11979 standards for intraocular lenses.

Biocompatibility Studies

Iloya conducted a battery of in vivo and in vitro acute and chronic toxicity tests thatestablish the biocompatibility of the lens materials. The biocompatibility studies wereperformed in accordance with the requirements in ISO 11979-5 to establish a completeprofile for the 101, material. The ocular implantation study was waived because ofexisting human clinical trial data wiIh the IOL material. Summaries of thebiocompatibility tests conducted are listed in Table I.

Table 1: Biocompatibility Testing

'rest Description Item Results and ConclusionsTested

Cytotoxicity C(olony Optic No significant cell lysis orformation, direct and indirect toxicity; NoncytotoxicCytotoxicity -Colony formation, Haptic Cell lysis and toxicity: milidlvdirect and indirect cvtotoxicCytotoxicity - Agar diffusion, Optic No significant cell lysis orindirect contact toxicity; NoncytotoxicCytotoxicitv- Agar diffusion, I [aptic No significant cell lysis orindirect contact toxicitvy NoneytotoxicCtotoxicity - MM el ution 1I0L No si gnitficant cell lysis or

toxicity: NoncytotoxicCytotox i ci ty- Inhibition of cell 1O1. 14% growth inhibition; Mildgrowth _____. ___t inhibitor of cell growth

PMA P080004: FDA Sunmmarv of Satet . and Effectiveness Data page 3

Test Description Item Results and ConclusionsTested

Genotoxicity - Ames Bacterial Optic Did not cause a positiveReverse Mutation Assay increase in the mean number of

revertants per plate;Nonmutagenic

Genotoxicity - Ames Bacterial I laptic Did not cause a positiveReverse Mutation Assay increase in the mean number of

revertants per plate;Nonmutagenic

Genotoxicity -Chromosomal Optic Induced no clastogenic activityaberration in the in vitro human

lymphocyte metaphaseanalysis; nongenotoxic

Genotoxicitv -Chromosomal Haptic Induced no clastogenic activityaberration in the in vitro human

lymphocyte metaphaseanalysis; nongenotoxic

Maximization Sensitization Optic The extractants showed noevidence of causingsensitization in guinea pigs;Nonsensitizing

Maximization Sensitization I-laptic The extractants showed noevidence of causingsensitization in guinea pigs;Nonsensitizing

Nonocular implantation - 7 and Optic Tissue reaction; mild irritant28 days (mild)Nonocular implantantion - 7 and I laptic Tissue reaction: mild irritant28 days (mild)Ocular implantation WJWaived - I urman evidence of

IOL material and ocular tissuetolerance

Nd:YAG Laser Cytotoxicitv IOL No cytotoxicity or leachables;Noncytotoxic

Test Extractable and Hydrolytic TOL No significant extractables: NoStability defects by scanning electron

microscopyTest Extractables by Exhaustive I eL 0.3594, extraction rate; LowExtraction extraction ratePhotostability Cytotoxicity I()L No signiticant residual(F-05-108) extracted; photostableCytotoxicitv - Growth inhibition 0I1. No significant cell lysis or(04Z099) toxicity; noncytotoxicCytotoxicity - Direct contact I-laptic No significant cell lysis or(1-)05 177) ______________ toxicity; 1noncytotoxic

cytotoxi city - Il utIon I laptic No significant cell lysis or(I'-05-178) j toxicity; noncytotoxic

PMA P080004: FDA Summary of Safety and BI'lectiveness lRita page 4

10

Test Description Item Results and ConclusionsTested _ _ _ _ _ _ _ _ _ _ _ _ _ _ _

Cytotoxicity -Direct contact IOL No significant cell lysis or(Y5J1 100 ) ___ ____ toxicity; iloncytotoxic

Cytotoxicity - Direct contact IOL No significant cell lysis or(Y6G054G) ___ _____toxicity;. noncytotoxic __

Cytotoxicity - MEM elution LoL No significant cell lysis or(Y6G053G) _____toxicity; noncytotoxic101, Extraction in Saline and -101. 0.25% extraction rate; LOWAcetone levels of extractables from

acetoneOptic Extraction Rate in Organic Optic From 0.10O to 0.44% ; L~owSolvent extraction rateI laptic Extraction Rate in Haptic From 0.10O to 0.44%: LowOrganic Solvent __extraction rateCytotoxicity - Colony formation AVBAA Cell inhibition at 0.3mgu/kgAcute Ocular Irritation AVA sN ifniicant reaction;

NonirritantGentoict -Ames Bacterial AVBAA 2 wefllsdsReverse Mutation AssayGenotoxicity - Ames Bacterial AVBAA Normal growth and colonyReverse Mutation Assay ma____ nube r; nonmutruagenicMaximization Sensitization -AVBAA No significant reaction:

_______ _____________________N on sensitizing

Acte Oral Toxicity AVBAA No death, no signs; No oral__ _ _ __ _ _ __ _ _toxicity __________

10 L intraocular lensAVBAA - aniline vinylbenzilIe anthiaquinone

Laboratory Studies anti Manufaeturin2

lData from engineering analyses dem onstrate the suitability of'the material and overalldevice design for use ill intraocular len-rses; these studies are slummarized in Table 2. TheadeqLC~tayof the manufacturing Ircsses, including sterilization, was established throughreview of the manufacturirng information in the PMA, as well as through on1-siteinspections.

Table 2: .[.aboratory Studies

Laboratorv Studies F___ est and ResultsOptical ~~~~~~Clear Optic Diameter, lDioptric P~ower (at

QO and 90'). resolution efficienicy (at 00 and9Q0') aind spectral transmittance passed the

______ ______ ~~~aceeptainc~e criteriaOptial: odultionTransfer All lenses had anl IT, Iof 0.-34 or better at

Function_(MTF) --___- ___ 1-00 I p/mmil.

PNMA P080004: F~DA Summ iary of Safety and Effectiveness Data p age- 5

Laboratory Studies _ Test and Results ___________

Mechanical: Dimensions Overall diameter, sagitta, vault height, opticbody diameter. All dimensions were withinthe designed acceptance criteria

Mechanical: Optic decentration At a I10mm compression diameter, all lenseshad a decentration of 0.42mm or less

Mechanical: Optic Tilt The average optic tilt of a 20.OD) lens at the_____ ____ ____ ____ ____ ____ compressed diameter was 0.630

M~echanical: Loop pull strength The force to pullI the haptics exceeded IN.Mechanical: Fold and Recovery Lenses were free of cosmetic defects andTesting any permanent changes to the optical or

mechanical properties of the lens when heldin a folded state in the [ loya - IS Injector

________________________System for a minimum of 3 minutes.

Mechanical: Surface and Bulk No lenses exhibited -cosmetic defectshomogeneity

Sterilization, Packaging, Shelf Life and Transport StabltyLThe objective of the sterilization, shelf-life, and transport stability studies was to establisha complete microbiological profile for the iSpheric Lens.

Table 3 summarizes the tests conducted to establish the microbiological profile of thepackaged iSpheric Lens.

Table 3: Sterilization, Packaging, Shelf Life & Iransport Tests

Sterilization Validation Test ConclusionsSterilization Revalidation: ThSecm isong and reqrialificationRecommissioning of Ethylene was performed according to 1SOI0 1135-1:Oxide Gas Sterilizer 1994, "Medical devices -Validation andRequalification: Evaluation Of routine control of ethylene oxidePhysical and Microbiological sterilization" Bande were within acceptableQualification of Sterilizer limits.

Steri lant Residuals: The report of residUal I £ and BCT J-Ethylene Chlorohydrin (ECI-l) analysis xvas within acceptable limits in

accordance with [SO 10993-7:I 995/R(?0() I ), "13iologi cal evaluation ofmedical devices. Part 7: E'thylene oxidesterilant residuals."

Ehlene Oxide (ID [h eort Of r esidual1 I £0 analy'1sis waIswithin acceptable limits in accordance with

ISO 1 1 35I:994. "Medical devices -

\alidation and rotutin control of ethylene_____________ ox~~~ide sterilization.''

Bacterial Endotoxin l'estingF EdtxiIeelsrebownmaII t

as set by the Agency for medical devices___________ ~~and accordi ng to Li PJ)

1NMA LP0S0004: FDA Summiary of Safety and Effectiveness D~ata page 6

Bacteriostasis and Fungistasis No antimicrobial activity was exhibitedTesting with testing performed according to USP.

Package Integrity Tests Test ConclusionsEnvironmental and Microbial The results are deemed acceptable.Challenge p e r__ o r-daoringtA _T

Seal Integrity Tests Testing was performed according to ASTMF88-00, "Standard lest Method for SealStrength of Flexible Barrier Materials"and the results are deemed acceptable.

Dye Penetration Tests Testing was performed according to ASfMF 1929-98, "Standard Test Method forDetecting Seal Leaks in Porous MedicalPackaging by Dye Penetration" and theresults are deemed acceptable.

Burst and Creep Tests Testing was performed according to ASTMF 1140-00, "Standard Test Methods forInternal Pressurization Faailure Resistanceof Unrestrained Packages" and the resultsare deemed acceptable.

Shelf Life and Transport Test ConclusionsStability TestsAging Studies Testing was performed according to ISO

11979-6, "Ophthalmic implants-Intraocularlenses-Part 6: Shelf-life and transportstability" and was acceptable for a 60month shelf life.

Conclusions:The overall results of the preclinical tests were acceptable from biocompatible,physiochemical, optical, mechanical and microbiological perspectives.

X. SUMMARY OF PRIMARY CLINICAL STUDY

The applicant performed a clinical study to establish a reasonable assurance of safCtyx andeffectiveness ofl0. implantation with the lLoya iSpheric"' Model YA-60BB 101.. in theUS under IDE # G030239. Data from this clinical study were the basis for the PMAapproval decision. A summary of the clinical study is presented below.

A. Study Design

[he objective of this clinical study wxas to assess the safety and effectiveness of the I lovaiSphcri c" Model YA-60BB 1I1, 1for the visual correction oftaphakia in adult patients inwhom a cataractous lens has been removed. The clinical study was conducted in a singlephase. A total of 617 eyes (412 were primary eyes and 205 were secondary eyes) wereenrolled by and followed through 12 months postoperative after which their results wereassessed by FDA.

PMA P080004: F L)A Suim mary of SalIty and I[ffectiveness Data page 7

Patients were enrolled in the clinical study in a non-randomized fashion at 11 clinicalsites with their results compared to literature controls, namely the FDA "Grid" of cataractsurgery results. In Stark et al. Ophthalmology, 90(4):3 11-317), FDA published a grid ofhistorical clinical data established from review of 45,543 eyes implanted with IOLs PMA-approved before 1982. FDA adopted the Grid which includes adverse reaction rates, sight-threatening complication rates and visual acuity results, for comparison to new lensmodels. Based on the analysis of the detailed data presented in the PMA, it was determinedthat the clinical performance of the Hoya iSphericTM Model YA-60BB Intraocular Lensescompares acceptably with the grid of historical data. A medical monitor, contract researchorganization (CRO), and IRB oversight were utilized in this study. [he study began onFebruary 25, 2004 and the final patient was enrolled/implanted on July 20, 2005.

Statistical Analysis PlanStudy sample outcomes have been stratified and mean values for effectiveness and adverseevent parameters evaluated to examine intra-study variations. Furthermore, the overallstudy data has been compared to the FDA Grid values using parametric Chi-SquareGoodness of Fit testing to determine if statistically significant differences exist. The levelof significance for all statistical evaluations will be P-0.05. Therefore, any within-groupscomparisons or comparisons of the study data to the literature controls in which the level ofsignificance is less than or equal to 0.05 are considered statistically significant.

1. Clinical Inclusion and Exclusion Criteria* Inclusion Criteria:

o Adult patients with cataract who were eligible for phacoemulsificationcataract extraction of the lens through an incision of approximately 4mm, and primary implantation of a posterior chamber intraocular lens

a Patients must have had no pre-existing ocular conditions that precludethe ability of the created eye to achieve best-corrected visual acuity(BCVA) of 20/40 or better after JOE implantation.

o Patients must hav e been at least 21 years of age.o Patients must have signed a written informed consent form.o Patients must have been able and willing to return for scheduled

follow-up examinations after surgery throughout the 36 month study.

* Exclusion Criteria:o Patients with a hi story ofOFr clinical signs of any of the following

sight-threatening conditions:Previous Retinal Detachment or retinal pathology in operativeeye, onlyMacular Degeneration in either eveMacular Edema in either eyePersistent h'itis/liveitis in operative eve, onlyIU ncontrol led Glaucoma or Under current treatment forglaucoma ill cithcr eye

* Significant Corneal Disease in operative eye, onlyP iroliferative Diabetic Retinopathy in either eye

o Patients who had previous ocuhlr surgery, of lany kind, within the last 6months or patients who have had previous ocular surgery at any time

PNMA P080004: FDA Surnrmary of Salety and [Lielctiveness Data page 8

and who did not have potential BCVA after cataract extraction/[OLimplantation of 20/40 or better

a Patients who had best corrected vision worse than 20/200 in the felloweye.

o Patients with serious (i.e., life threatening) non-ophthalmic diseasewhich may have precluded study completion.

o Patients who had undergone previous cataract extraction andintraocular lens implantation.

o Patients unwilling or unable to sign the IRB-approved informedconsent document for the study or who could not or would notcomplete the study's examination schedule.

a Patients who were currently enrolled in another clinical trial, or whoexited a clinical trial within the last 30 days.

2. Follow-up Schedule

All patients were scheduled to return for postoperative follow-up examinations at 1-2days, 7-14 days, 30-60 days, 120-180 days, and 330 to 420 days postoperatively.

Preoperatively, patients scheduled to undergo cataract extraction and intraocular lensimplantations were screened for eligibility, and eligible patients were evaluated to obtaina medical history and to establish a baseline for ocular condition.

Postoperatively, patients underwent a complete ophthalmic evaluation at regularlyscheduled intervals to assess the condition of their eyes and visual function for 12 monthsafter their cataract surgery. Adverse events and complications were recorded at all visits.

Clinical evaluations included Best Corrected distance visual acuity (BCDVA), manifestrefraction. intraocular pressure measurements, and slit-lamp ophthalmic evaluations todetermine adverse events or postoperative complications. A sub-study to address thepotential For diminution of color vision due to the yellow tint of the TOL optic wasconducted on 50 patient eyes. A Farnsworth D-1 5 Color Vision assessment, whichinvolves a timed test to arrange color-coded disks, was performed preoperatively and attwo postoperative exams to detect any color vision abnormalities

Adverse events and complications were recorded at all visits. [he key time points areshown below in the tables summarizing safety and effectiveness.

3. Clinical Endpoints

The major endpoints are as discussed in the FDA draft Intraocular Lens GuidanceDocumcnt dated October 14. 1999.* Safety:

Adverse Events (Cun:ulative and Persistent) as categorized and evaluatedby the Fl)A grid.

* Ftfectiveness:o Best Spectacle Corrected Visual Acuity (BSCVA) %of primary eyes

(All eves)> 20/40.

PMA P080004: FDA Summarv of Safety and Effectiveness Data page 9

J5

o BSCVA -- % of primary eyes ("Best Case" eyes) Ž20/40, as described byFDA draft Intratocular Lens Guidance Document (and ISOI1197907:2001 (E)) and compared to FDA grid.

B. Accountability of PMA Cohori

For this PN4A, the 446 patient eyes (300 primary eyes and 146 fellow eyes) thatcompleted the Form 5 exam in adherence with the study protocol exam windows wereused to assess the safety and effectiveness of the 10L. The Primary Cohort excludes148 "Incomplete" patients who had missed a follow-up visit or were seen outside of theprotocol-specified windows (full data sets are provided for these patients). All but 9 ofthese "Incomplete" eyes had a Form 5 visit on record. Separate effectiveness analysis ofthese 148 eyes demonstrates that that there was no selection bias regarding BCVAresults at each study site with respect to classification of patients as Incomplete. Thesafety analysis included all 616 patients (including the "incomplete patients"). Table 4provides a summary of patient ac.countability.

fable 4: Accountability by Post-operative Visitiota] Eyes

ITotal NumrberC0kenllmed)

______________________________________ I~~~~~~~~~~~%aLecountabilityl _______ _.

Patient status Linrc Iled FomI Fr 1 -2 Form 3 Far-nt 4 Fiil Tis 5F- orrm- b n 7617 1-2 davs weeks 1-2 months 4-6 monthlls 1 1-14 22-36 33-39

__________________________________________________ __________________ months monthss months month

Available 614 613s 610 604 584 31l 506(99,5%) (99.7%) (91(9%) (97.9%) (94.7%) (86.1%) (82.0%),,

1614/616=- 16l5/616= [ 610/616= [604/613=- [584/59-5- [53 1/566= 1506/521=99.7' 1 99.8 %] 99.(%I 98.5%]l 98.2%]~ 93.8%j 97.1% I

Missing patients:Discontinued I I I 4 22 -5! 96

(0.2%) (02%)O (0.2%) to(16) (36) 83) (15.60,%,)MIsS~'inc a SChdledILI~ visit butl s~eena I 021)later (0.0%) (0.0%) bit2%) (0.0%) ( 0.0%,) (0.3%) (0.2`%)Not seen butl accounted liv 2 I 4 9It1 28 3

(0.3%') (2'it) (O.6%) (I5½ (I.% (45% (0%l ost to bfolow-up 0 )I0I I

(0.0%) (0.0%) (0.~~~ ~~2%) to(0.0) ( 0.0%~) (0.8) I18%Active 00f I1

_____________________ 10.~to0%) (4~~0)-s) (0.10) (01 (011)(01)01%l~iseortinkred partieints airc those who have astuds-li tr,Pat i erts who are miss in a a a sec edcaled v~is it have a flater fbtioW-tip/i nIseheettrle~d bib lPatients whlo are not see- bitt aiccounted for have a form which indie ttes patient is uttavailablc bit eotttifcina11 inl hIe studeIPatiecuts lost to fo I low-u pdii ot 1 , have a torn-n are past die lbor tlte visit, mid the (hlae of lbheir latest lorm, is be tore ttse nsew 'w-tndowActive patients are those who have not reached the time aissociated vt th the torn,P lerceeit accourntabilits is thre U~lisbei rvatilalble/(L~notltcd dtiscojitimt cl - active) __________

C. Studv Population IDcniographics and Baseline Parameters

The demographics of the studylpopulation are typical foi an 101. studyV performed11CC inlthe US. The population at risk~ for dcevilopino vistlally-disabling( cataracts andneeding- cataract surgery is tvpically elderly; the elderly population generally has ahigher proportion of females to -nales. The average age for the 61 7 patients enrolledinl this studyI Was appro0ximjately '70 Years at the time of SUrgery andI 62.700 of the

emold patients w efiemtal with 373% beit, umale. 'I Il td 7optulation did notexc lode patients onl the basis of genider or gender-related pathology. [he study

I'MA P080004: F DA Summ11aryV of Safety andic Effectiveness Data page 10

population was approximately 93% Caucasian or Hispanic; 4.2% were African-American, 2.9% were Asian. All patients who met the Inclusion criteria and receivedthe study iOL were included in the study analyses. One patient did not get includedin the analyses after enrollment because the patient did not receive the study IOL dueto rupture of the posterior capsule before IOL implantation was attempted. Table 5provides a summary of population demographics and baseline parameters.

Table 5: Patient Population Demographics and Baseline Parameters

All Eyes Primary Eyes Fellow EyesN =617 N = 42 N = 205

Gender: N (%) N (%) N (%)Female 387 (62.7%) 256 (62 1%) 13 (63.9,%,)Male 230 (37.30%) 156 (37.9%) 74 (36.1%)

Age (years) MeanP (S.D.) Mean (S.D.) Mean (S.D.)Range Range Range

Overall 70.5 (9.3) 70.4 (9.4) 70.7 (9.1)38.2 -89.8 38.2 89.8 38.2 -88.9

Female 70.5; (9.0) 70.5 (9.3) 70.4 (8.5)40.4 89.8 40.4 -89.8 41.7 889

Male 70.5; (9.6) 70.2 (9.4) 71.2 (10.0)038.2- 88.3 38.2 88.2 38.2 -88.3

Patients by Age N (%) N (%) N (%)<50 17 (2.8%) I (2.70) 6 (2.9%)50-59 66(10.7%) 47(1 1.4A%) 19 (9.3%)60-69 186 (30.2%) 125 (30.3%) 61 (29.8%)70-79 266 (43.1%) 172 (41.8%) 94 (45.9%)>80 82 (13.3% 57(13.8%) 25 (12.2%)Ethnicityv N (%) h % N (%)N}lispanic/Latino 32 (5.2%) 22 (5.3%) I0 (4.9%)Not Hispanic/LIatino 585 (948%) 390 (94.7%) 195 (95.1%)Race N ( %) N (%) N (%)Asian 18 (2.9%) 11 (277%) 7 (3.4%)Black/African American 26(4.2%) 20 (4.9%) 6 (2,9%)White 573 ('92.9%) 381 (92.5%) 192 (93.7%)

I). Safety and Effectiveness Results

1. Safetv ResultsSafety was evaluated with regards to specific cumulative adverse event rates andpersistent adverse events rates as specified in the FDA Intraocular LensGuidelines, 1996 and ISO 11979-7 (Ophthalmic implants - Intraocular lenses -Part 7: Clinical investigations). Primary safety analyses are based on data from allenrolled patients with follow-Lup to at least one-year post implantation. Ihe FDAhistorical control is derived from weighted averages of the data from. 13 largeclinical i nvestigations of' O)Ls (anterior and posterior chamber) between March1988 amnd .l une 1991. ihe pooled sample size for these clinical investigations was5162 adverse events.

Cunmulative adverse events arc those Which occurred at any time during thepatient's postoperative course through Form 7 (approximately 3 years post-operatively). Although ctumulative adverse events were tabulated if they were

PMA P080004: 1Fl)A Sumrmary oflSafety and ETfectiveness Data page II

reported at any time through Form 7, the FDA Grid rates for persistentcomplications are listed for events that are present at the 12 month exam (Form5).

The adverse event rates were not statistically significantly different from thehistorical FDA grid control Population rate for all of the listed cumulative andpersistent adverse events.

The key safety outcomes, cumulative and persistent adverse events, for this studyare presented below in Tables 6 and 7.

Table 6: Cumulative Ocular Adverse Events for all Enrolled EyesCompared to FDA Grid (N-616)?

Adveie Even/vHoya YA-60BB FDA Grid

N (%) N (Cumulative lndophthalnitis 2 0,104

Cumulative flyphema 0 (0%) 2.2%

Cumulative I Typopyonl I (0.2%) 03%

Cumulative Lens Dislocation 2 (03%) 01%*

Cumulative Macular Edema 24 (3.9%) 3.0%"_

Cumulative Pupillary Block 1 (0.2%) 0.1%f

Cumulative Retinal Detachment 2 (0.3/<) I,

Cumulnlive Secondary Surgicl I.ntc1 t ention 9 (1 . 5) 0.8%'

L ,ens repositioning 2 (03%)

Lens removal (any reason) 2 (

*Differences are not statistcally significanti'One patient was enrolled in the study but did not receive the study lOt, due to surgicalproblems before lens implantation.

Table 7: Adverse Events Reported at 12 Months Postoperative

Hoya YA-60BB FDA Grid

N (7) N (%,,)Persistent Corneal lIdema ( 3

Persistent Iritis 3)2 )3

Pers istent MacuLlar I 'OemIa)

Pcrsistent Rlaiscd JIOP Reqlulring

Treatt nent (0%)

PMA P080004: FDA Summary of Safety and Effectiveness Data page 12

** Persistent macular edema occurred at a rate of 0.8% which was statistically insignificant from theFDA Grid rate (X2 - 0.46 P>0.05).

The adverse event rates were not statistically significantly different from thehistorical FDA grid control population rate for all of the listed cumulative andpersistent adverse events. Of note, is that during the IDE, there were two cases ofendophthalmitis (one culture positive and the other "sterile"). With two cases ofendophthalmitis reported among the 616 total implanted patients (inclusive of the22 "discontinued patients" and 148 "incomplete patients"), the rate is 2/616(0.3%). The FDA grid has a rate of 0.1% for comparison but a Chi-Squareanalysis (X 2 0.73. P>0.05) indicates this difference is not statistically significant.These cases are not believed to be device related.

Two patient eyes had the Hoya lens explanted during the study; both of thesewere primary eyes (0.3%). One was explanted due to acute inflammation and tileother was explanted when tha patient went to a non-study surgeon and requestedexplant; no reason for explantation was provided by explanting surgeon.

Two cases of lens dislocation apparently related to iatrogenic causes werereported.

A total of 9/616 (1.5%) of enrolled eyes implanted with the study IOL eyesunderwent a secondary surgical procedure after implantation with four of thesecases being patients outside of the PMA Primary Cohort. None of the secondarysurgical interventions can he directly related to the study IOL.

Fifty seven (57) of 616 eyes ,(9.3%) underwent an Nd:YAG posterior capsulotomyfor Posterior Capsular Opaci ication through three-years of postoperative follow-up.

Postoperative Inflammation in PMA Primary Cohort Fyes

Non-routine postoperative inflammation was defined as:lForm 2 - Cells, flare or iritis is considered routine if not rated moderate orsevere; regardless of whether patient is on steroids or NSAIDs.

Form 3 T race cells, flare or iritis is considered routine if patient is receivingsteroids or non-steroidal anti-ir1flamrnatory d-rugs NSALDs. If paitient is nolonger on steroids or NSAIDs, patient may have mild cell. flare or iritis. Anyreport of cells, flare or irinis that is moderate or severe is not routine,regardless of medication status.

lForm 4 or later - Cells, flire or iritis should be absent. Should be zero byForm 4.

Form 2: 1 .6% reported non-routine postoperative inflammation.None ofthese eyes reported macular edema or other adverse events. I00%achieved 20/40 or better BC\/A at Form 5.

PMA P080004: FDA Summary of Safety and Eff1ectiveness Data page I3

Form 3: 0.7% reported non-routine postoperative inflammation. One of these eyes(06-044B) represented a cas,: of bacterial endophthalmitis approximately sixweeks postoperative, but 100% achieved 20/40 or better BCVA at Form 5.

Form 4: No eyes met the criteria for non-routine inflammation at Form 4.

Form 5: No eves met the criLeria for non-routine inflammation at Form 5.

2. Effectiveness ResultsResults for distance Best Corrected Visual Acuity (BCVA) are shown in Table 3.Of the 446 patient eyes, 98.o7% reported a BCVA of 20/40 or better one year aflersurgery and 52.8% reported a BCVA of 20/20 or better. Table 8 contains asummary of BCVA results.

Table 8: Best Corrected Visual Acuity, (300 primary eyes and 146 fellow eyes)

Form 1Pre-Op (N=445) Form 2 Form 3 Form 4 Form 5(N=446) Pinhole VA N_443} _ ( Nx445 N445 (N445)

BCVA

20/1 5 I1(1.4%) 13 (2.9%) 31 (7.0%) 32 (7 2%) 35 (7.9%) 29 (6 5%)

20/20 33 (7.4%) 90(20.2%) 211 (476%) 246(55.3%) 260(584%) 235 (52.8%)

20 25 58 (13.0%) 106 (23.8%) 107 (24.2%) 102 (22.9%) 101 (22.7%) 110(24.7%)

20/30 1(8 (2422%) 93 (20.9%) 56 (12.6%) 42 (9.4%) 38 (85%) 47 (10.6%)

20/40 1 17 (26.2%) 81 (18.2%) 26 (5.9%) 17 (3.8%) 7(I 6%) 18 (4.0%)

Tota120/10 orbetter 317(71.1%) 383(86.1%) 431 (97.3%) 439(987%) 441 (98.7%) 439(987%)

I'otad Nvorsc[han 20/40 129 (289%) 62(139%) 12(2.7%) 6(1.3%) 4(1 3%1 6(1.3%1

Total 146 445 443 445 ,45 446

Table 9 shows best corrected visual acuity for primary eves.

fable 9: Best Corrected Visual Acuity, Primary Eyes by Form

PMA P080004: FDA Summary of Safety and lffectiveness D)ata page 14

70

Form IPre-Op I (N=300) Form 2 Form 3 Form 4 Form 5

:(N=308 Pinhole VA N(N=298 (N=299 1 (N3001 (N-30)

BCVA

20/1 5 (0 (0.7%) 7 (2.907o) 18 (5.9%) 18 (6.00%) 18 (6.0o) 17 (5.7%)

20/20 14 (25.7%) 55 (15.6%) 143 (453%) 166 (55.5%) 173 (57.7%) 156 (52.0%)

20/25 30 (22.7%) 74 (25.0%) 74 (28.0%) 64 (21,4%) 71 (23.7%) 73 (24.30,,)

20'/30 64 (23.0/%) 55 (18.8,) 36 (1117%) 35 (117%) 29 (97%) 35 (11.7%)

20/40 84 (17.3%) 59 (20. 1 %) 16 (499%) 13 (4.4l%) 6 (2.0%) 15 (5.0%)

1ota 1 20/40 orbetter 192(89.3%) 250(833%) 28 (96.3,0) 296(99.0%) 297(99.0{) 296(98.7%)

Ilotal worsethan 20140 108(107%) 50(16.7%) 111(37%) 3 (1.0%) 3(1.0%) 4 (1.3%)

Total 300 300 298 299 300 300

Table 10 shows Best Corrected Visual Acuity Data for Best Case patientscompared to FDA grid Best Case Patients. All the patients in the PMA PrimaryCohort were Best Case Patients. Consequently. the Sponsor did not provide aseparate clinical analyses for Best Case Patients in this PMA (no separate tablesfor Best Case patients) since they would be identical to the BCVA tables for allP1MA Primary Cohort patients. Thus, the rate of 20/40 or better BCVA for BestCase patients is identical to the result for all PMA Primary Cohort patients, or98.7% which compares acceptably with the FDA Grid for Best Case patients of96.7%.

Table 10: Best Collected Visual AcUity Data foir Best Case patients

<60 years 60-69 years 70-79 years >80 years All Iatients(N=51) (N= 144) (N= 198) (N=53) (N-445)

BCVA

20 /IS5 7(13 .72%,,) 15 (10.4%) 7(3 6(,) 0100%) 29 (6 5'%,)

20/20 31 (60.,S%) 84(58;3%) 94 (47.7%) 26(41 lt,) 235 (528')

20/05 8 (15.7%) 31 (2; 5%',) 55(2799%) [6(30.20) 110(2 17%,)

20/320 (3 90,) 1 (7 6%) 27 (137%) 7(1320¢,) 47(10.60)

1 (2(13/,,) I (0.7%) 13 (6.6%) 3 (5 7'%') 18 (4.0)

Total 20'/4( orbetter 49 (96[ 1) 142 (98 60}) 196 (99. 5") 52 (98 I%) 139 (98

Iotal Nvoisc[I, 20/10 0 (3 9~.) 2 I 'I%i I (0.55%1) 11.9%) 61

'ITotal 51 1[44 197* 53 15

FDA Grid 98 >0' (6 97.5% 9 1. 96

*t3V.VA not repotled lot (lm ie patient

PMA P080004: [:)A Surnmmary of'Sai'tv and Effectivencss Data page 15

9i

Only 6 patient eyes enrolled in the study failed to achieve BCVA of 20/40 orbetter at 12-14 months postoperative. All of those eyes were Best Case patients(i.e., patients with no preoperative ocular pathologies or macular degeneration atany time during the study).

3. Slubg~roup AnalysesFor the purposes of the color vision sub-study, the sponsor assumed that a clinicallysignificantl level of post-op color vision defects with the Farnsworth D-1I 5 would be1000 of patients. To obtain a confidence interval of +7.5%~ at the 9500 confidencelevel, they calculated a minimium sample size of 43. Alloxving a small number ofpatients for loss to follow-up., a total of 52 eyes were enrolled in the color-visionsrib-study and 44 of them met the protocol criteria and completed both thepreoperative and postoperative testing.

None of the eyes that passed the test preoperatively and qualified for the sub-studyalso failed it both times postoperatively; 100% of these patient eyes passed the colorvision test preoperatively and at least once postoperatively. None of the patients thatreceived the Hoya 101. xvith yellow-tint requested explanation of the lens due to acolor vision disturbance. These data indicate that the Hoya iSphcricTM Model YA-6OBB Intraocular L enses had no significant effect on color vision outcomes afterimplantation.

XI. PANEL MEETING RECOMMENDATION AND FDA'S POST-PANEL ACTION

In accordance with the provisions of section 515(c)(2) of the act as amended by the SafeMedical Devices Act of 1 990, this ENIA was not referred to the Ophthalmic DevicesPanel, an FDA advisory committee, for review and recommendation because theinformation in the PMA substantially duplicates information previously reviewed by thispanel.

XII. C'ONCLUJSIONS I)IRAWN FROM PRECLINICAL AND CLINICAL STUJI)IES

A. Safetv Conclusions

THie rates of adverse events associated with the F-loya iSpheric" Mode! YA-60BB3 IOL. iscomparable to or lower than the rates associ atecl with the historical control p)opulation Of

lOLs.

B. Effectiveness Conclusions

The I-Ioya iSpherjCT Model YA-60BB 10L. provides comparable or better distancevisual aIcuity results compared to the rates aissociated with the historical controlpopulation of TO1-s.

C. Overall Conclusions

'The data in this application support the reasonable assurance of safety andeffectiveness of this device when used in accordance with the indications Ior use.

PMNA P080004: FDA.S urn mary of Safety a id F fflectiveness [)a ta pa~ge 1 6

XIII. CDRH DECISION

CDRH issued an approval order on September 26, 2008.

The applicant's manufacturing facility was inspected and found to be in compliance withthe device Quality System (QS) regulation (21 CFR 820).

XIV. APPROVAL SPECIFICATIONS

Directions for use: See device labeling.Hazards to Health from Use of the Device: See Indications, Contraindications,Warnings, Precautions, and Advcrse Events in the device labeling.

Post-approval Requirements and Restrictions: See approval order.

PMA P080004: FD)A Sumnmoary of Satity and Effectivencss Data page 17

-72